Dear Internet: Please Mark this Prediction – Autism Rates will Rise Exponentially in Nigeria over the Next Five Years

LAST FRIDAY, I LISTENED TO an episode of Dr. Sanjay Gupta’s show on CNN, “Vital Signs“, in which he speaks with locals about the success in launching a polio vaccination campaign. Polio has been a real problem in Nigeria, where local customs have made the adoption of vaccinations difficult. Anything foreign can be made to be seen as a threat, and suspicions run deep. To eradicate polio in Nigeria, Sanjay says, a remaining 3 million children must be vaccinated.

The statistics on polio in Nigeria?  Zero (0) cases in three years (WHO/INT). Nigeria has been removed from WHO’s list of three countries in which polio in endemic. Is it  coincidence that CNN ran this story on the same day as the public was protesting vaccine safety research fraud at the CDC?

Watching his show, Sanjay made it seem like polio was everywhere. He also lead the audience to believe that every child in a country must be vaccinated, or polio cannot be wiped out…

Most importantly, I could not help wondering, while polio is certainly worth eradicating, once vaccines become more widespread over the next five years due to the success of this program, what will happen to autism rates in Nigerian children over the next five years?

Autism rates in Nigeria were 0.7% three decades ago (Bakare et al., 2012).

In 1970, autism rates in the US were also very low – 1 in 2500. As the CDC added more and more vaccines to the pediatric schedule, the rates increased. Although thimerosal was removed from pediatric vaccines in 2001, the schedule was also shifted simultaneously to include infants aged 0 – 3 years. Historically, vaccines were avoided in infants. So, although the removal of thimerosal should have reduced the incidence of autism, ADHD, and related outcomes, the dosage of aluminum, another neurotoxin, was increased at an age when brain developmental processes should be most protected. Further, thimerosal is still be used in vaccines used in developing countries.

Autism rates are now 1 in 68 in the US – some estimate have it as high as 1 in 50. The increased from 1 in 2500 to 1 in 68 cannot be explained by improved diagnosis, nor can it be explained by the DSM-V lumping of many conditions other the “Austism Spectrum Disorder”. The type of autism driving the increase over this time was regressive autism – all but removed from the DSM-V and replaced with “childhood disintegrative disorder”. One type of autism, Rett Syndrome, was removed from the spectrum altogether because the molecular etiology was known. Unfortuntely, only some, but not all of children with Rett Syndrome have mutations in the gene that has been shown to cause Rett Syndrome. And merely because a disease has a genetic component does not absolve the environment. We do not re-name breast cancer cases as something other than breast cancer when a gene is found that contributes to the risk of breast cancer.

Two very large studies have also determined that genetics and environment contribute more or less equally to the risk of autism. A breakdown of concordance rate by gender in the study also indicates room for environmental factors. Male identical twins showed 77% concordance, while identical twins showed 50% for female identical twins. The rates among fraternal twins were 31% for male pairs and 36% for female pairs (Hallmayer et al., 2011).

Compared to the proportion of liability explained by genetics for “strict” autism (37%) and for ASD (38%), a much larger proportion of causal influences was found for shared environmental factors (55% for autism and 58% for ASD). These results suggest that a good deal of research focus on environmental factors is needed.

A much larger study (Sandin, 2014) involving 2,049,973 Swedish children (born 1982 through 2006) included 37,570 twin pairs, 2,642,064 full sibling pairs, 432,281 maternal and 445,531 paternal half sibling pairs estimated heritability of autism at 50% and ASD at 54%. They found that individuals with an autistic sibling has a cumulative probability of an ASD diagnosis at age 20 of 13%, compared with 1.2% for individuals without an ASD sibling. Concordance (estimated by a tetrachoric model) was found to be 54% for identical twins, 25% for fraternal twins, 11% for siblings.

Considering the full population, which included a term for shared environment, contribution from shared environmental factors was estimated to be 4%. Overall, non-shared environmental factors were more important (54% variance explained) than heritability (42%). Using all twins only the heritability was estimated to 52%; some of this may be due to hidden shared environmental factors

Much more on that when I finish my book, “Genetic and Environmental Causes of Autism”.

Either way, genetics also cannot explain the increase – gene frequencies do not change in less than 1/2 of a human generation – and thus we are stuck looking for a plausible explanation.

There is an immense body of literature supporting autism-like features developing in animal studies – and flaws in the most recent studies showing no effect of thimerosal. A recent study in  Proc. Nat. Acad. Sci. in which a handful of macaques were dosed with thimerosal equaling the 2013 pediatric schedule was woefully underpowered (i.e., did not a large enough sample size) to detect an adverse event effecting less than 2% of the population with a diverse component of genetic risk. The immense body of knowledge demonstrating both thimerosal and aluminum as neurotoxins can no longer be ignored (see “Thimerosal: Let the Science Speak“).

The vaccination program in Nigeria is an uncontrolled experiment. Rates of autism are cited as high as 1 in 88. I predict that autism rates will increase even further as a result of the increase vaccinations to come, as more children are vaccinated there given the push to popularize vaccines. This prediction is being made on October 26, 2015 based on the fact that the CDC found a 240% increase in the risk of autism due to vaccinations, but omitted the results from their study (so says Dr. William Thompson of the CDC).  They also removed from the manuscript the result indicating increased risk for idiopathic autism due to vaccines (source: Dr. William Thompson, CDC). If, by October 2020, the autism rates in Nigeria increase from 1 in 50 to 1 in 25, or 1 in 15, or 1 in 10, then no one can say it was not vaccines.

Oh, and let’s not forget that autism rates are still increasing in the US.

We have a choice to make in terms of vaccine safety research. We can either reform vaccine research at the CDC, or we can allow them to perform another uncontrolled experiment on a trusting, unwitting population.

How You Can Help

In 2015, I created IPAK – the Institute for Pure and Applied Knowledge.  IPAK performs research in a manner that is independent of profit motives. One of the Project Areas that IPAK was created to focus on is Vaccine Safety Science Reform. By “Reform” we mean hold CDC scientists to the same standards that non-CDC scientists are held.

Requiring independent peer review of study designs and data analysis plans before any CDC conducted or funded Vaccine Safety Research study is conducted. The rest of biomedical science is subjected to external, independent peer review, but the CDC does not have to have their research plans approved. They approve of their own research plans.

Requiring 5 independent Universities to analysis the data from all Vaccine Safety Research Studies (3 by lottery, 2 by competitive research contracts).  When the CDC’s self-approved data analysis plans lead to results that do not fit their policy that vaccines are safe, they change the plan, says Dr. William Thompson of the CDC (See “CDC Whistleblower“).

Requiring that the Vaccine Board be dismissed and replaced by MD’s and PhD’s with relevant background, nominated and elected by a Vaccine Safety Congress of parents of children injured by vaccines. One Vaccine Board director owned the patent for a vaccines, got it approved (via his own vote) and then sold the patent for millions. That would be Dr. Paul Offit, who made a mockery of rational discourse on vaccine safety by claiming that a baby could tolerate 100,000 vaccines at once.

-Make it illegal for CDC, FDA, PHS, and NIH employees to obtain jobs in Pharma or any industry that would benefit from their policy making while employed by the Federal Government. Take Dr. Julie Gerberding, former Director of the CDC, who took a job at Merck after leaving the CDC. She recently sold over  38,368 shares of Merck stock, making a cool $2.3 million.

Help IPAK work in this important area. Donate today. Your donation will allow us to focus on making these necessary reforms a reality. You will receive a copy of “Progressive Science”, and a one-year membership in the Society for Pure and Applied Knowledge as thank-you’s for your donation.

Reference

Bakare MO, Ebigbo PO, Ubochi VN. 2012. Prevalence of autism spectrum disorder among Nigerian children with intellectual disability: a stopgap assessment. J Health Care Poor Underserved. 23(2):513-8. doi: 10.1353/hpu.2012.0056.

Hallmayer J., et al. 2011. Genetic heritability and shared environmental factors among twin pairs with autism. Arch Gen Psychiatry. 68:1095-102. doi: 10.1001/archgenpsychiatry.2011.76.

Sandin S, et al. 2014. The familial risk of autism. JAMA. 311(17):1770-7. doi: 10.1001/jama.2014.4144.

Postscript: Please watch this interview by Sanjay and Julie as they spin the link between autism and vaccines years ago away from one of the most clear-cut cases of an environmental trigger interacting with a genetic predisposition.  Especially when he says “Are we now ready to say there is no link” right after she said there was a link.  Very sad, as if the correct interpretation was allowed, we could have prevented millions of vaccine-related brain injuries.

causes

Why Dr. Sanjay Gupta is Dead Wrong In One Important Detail on Why Are We So Annoyed About Daraprim

Why Dr. Sanjay Gupta is Dead Wrong In One Important Detail on Why Are We So Annoyed About Daraprim

IN RECENT DAYS, more and more Americans have learned about the young CEO of a drug company, Turing Pharmaceuticals, who purchased an orphan drug called Daraprim and, overnight, raised the price (to consumers) of each pill from US$13.50 to US$750 (that’s over a 5,500% increase). The press interviewed Martin Shkreli, Twitter and Facebook blew up with anti-Shkreli posts. As the internet will do, it even gave him a particularly disparaging moniker – “Pharmaboy”.

A number of questions surround this increase. A number of questions also surround our society’s scale of response – from the individual to the Press – to this news of Turing’s overnight price hike.

Why are we so annoyed by this development, when so many other egregious examples of pharma megaprofits exist?

According Dr. Sanjay Gupta, Mr. Shkreli is embarking on a new way to raise investment capital for drug development.  Shkreli claimed that Daraprim could be improved upon, and therefore, the profits from the increased price would be rolled into the investment of new drugs.

The usual model of drug development, we are told, involves identification of a promising market, and a company (especially a new biotech company) raising venture capital. When asked by CNBC correspondent why his company did not go this route, Shkreli claimed that they had, in fact, raised a record-breaking US$90 million in venture capital.

(I can’t help but wonder if he can see that this point does not really help his case.)

I’ve done just a little research in this area, for my upcoming book “Cures vs. Profits” (World Scientific), and Dr. Gupta’s explanation seems to me more than a little off.  I recall from my research on how pharmaceutical companies either try, or do not try, to strike a balance between profit pressures and the need to bring forward the most effective treatments.  I wrote “Cures” in part in response to friends & family’s many questions about the medical industry, and the practice of medicine, including the rather blunt questions like “Tell us the truth, doctors don’t want cures – they want treatments, right, because they get more profit”.

Dr. Gupta is right that Mr. Shkreli”s brazen use of zero-risk price gauging irks us because he is trying to profit by an amount that most Americans feel is exhorbitant, and undeserved, for a number of reasons, such as:

There is no real risk on his part, the part of the company, or in investors. We do not like it when people get something for nothing.

We really, really don’t like it when people get something for nothing on the backs of other people in a way that we feel is unfair. We all know that when other cannot afford live-saving medicine, the buck is passed to the rest of us – either through increased insurance premiums, or via our taxes. Sure, companies have compassion programs, where they will provide treatments or test to some individual who are in need. But that raises the question – why increase the price in the first place, and put us all through this smoke and mirrors session?

HIV patients need this drug especially; given that there is no cure for HIV, he has a captive, long-term source of profit.

In contrast, Dr. Gupta’s claim that Mr. Shkreli is trying out a “new” way of raising capital for drug development is wrong in one extremely important detail.

It is not – by a long shot – new.

While being interviewed on CNBC, Mr. Shkreli himself provided a hint at a “everyone else is doing it” rationalization for his specific decisions. He said:

“We actually feel that this is a more appropriate price for Daraprim, uh
at this price Daraprim is still actually at the low end of what orphan drugs cost. We’re certainly not the first drug company to raise drug prices.

“Cures” is currently being copy edited. At the risk of spoilers, I am sharing an extended excerpt from the Preface. Because, well, Mr. Shkreli is correct, in a very big way, that Turing is not the first company to raise drug prices. Nor is Turing the first company to commit price gauging.

A friend of mine recently asked me “Doesn’t the free market correct for price gauging?”

To help understand the scope of the reveal by Daraprim missed by the media, I share here an extended excerpt from the Preface of my book. It contains some answers to these questions.  WARNING: THIS MAY LEAVE YOU WITH THE IMPRESSION THAT I AM ANTI-CORPORATE, OR EVEN AN ANTI-VAXXER COMMUNIST. I assure you I am not. There are many, many companies and medical doctors doing the right thing. The very good news is that most of the rest of “Cures” deals with what I consider bona fide good news on successes in translational research by some really great people whom I hope achieve great personal wealth from their discoveries – because they have imbued a deep sense of moralism into their business models.

That said, here’s your dose of medicine on why Dr. Gupta is incorrect.

From: “Cures vs. Profits: Successes in Translational Research”, World Scientific (2015?)

I have no particular agenda for this book other than to hopefully open up a dialog among all stakeholders in medicine with an eye on the positive. From the patient to the CEO, my goal to help bring about changes in our practices and policies that might lead to a larger number of effective and safe medical treatment options for doctors and patients to choose from, thus reducing death due to disease. Most importantly to me personally, these options should reduce human pain and suffering.

For some authors, it may be tempting to partake in the non-scientific near hysteria of people questioning the validity of western medicine. A counterculture exists in which suspicion, rumor, and idle speculation fuel the fans of discontent. If I were to write a book in that vein, I could expect disdain from my colleagues, whose esteem I hold dear… but I would expect to sell more books. No, this is no anti-medicine, anti-science book, either. It is instead an attempt to scrutinize objectively, and explain in simple, understanding terms, a number of important topics in medical research that I believe deserve a wider audience. For each topic, I began my research with an open mind. If, after my research, I have formulated an opinion, one way or the other, on a given topic, I say so. If I have formulated a conclusion, I make it clear. Where I have not, I call for more research.

Each individual medical doctor has taken the Hippocratic oath, by which they pledged to “First, do no harm”. Violations of this oath occur on a regular basis. Via this oath and in our placing our lives, and our children’s lives, in their hands, medical doctors share a sacred social contract with the rest of humanity. We place our esteem in them, we give them influence on social matters and public health matters, and we bestow upon them great wealth. While many doctors deserve the respect, social status, and wealth that come with their position, those guilty of egregious instances of abuse should be tried, and if convicted, sentenced.

Many Americans believe that for some doctors, the Hippocratic Oath is often made with some qualifiers in fine print, such as “First, do not harm (to profit)”. It is not hard to see why; medicine is projected to become a trillion dollar industry worldwide (Perkowski, 2014). The US is only one of two countries that permit, by law, direct-to-consumer marketing of pharmaceuticals (the other is New Zealand).

This book is not about heroes in medicine. That said, some rough estimates of lives saved by advances in specific medical practices and procedures paint the picture of medicine in a more beautiful palette. The website Science Heroes, for example (www.scienceheroes.com) reports that blood transfusions are estimated to have saved over 1 billion people. Their list goes on to report 109 medical heroes, estimated to have billions of lives saved. (The website is a companion to the book “Scientists Greater than Einstein” (Woodward et al., 2009; Quill Driver Books)).

So where does the concern over undue profits fit in? While it is true that we are all treated with options that, from a pharmaceutical corporation’s standpoint, were deemed potentially profitable, is this a mere fact of reality, or something else? Regardless of the nuances of motive, it means that many potentially effective drugs have not been brought to market. Why? Profitability is certainly a filter that has a homogenizing effect on medicine: Our treatment options are much more limited than they could be. This seems to be a perfectly acceptable norm to many.

On April 1, 2015, Anne De Groot, CEO of EpiVax, testified before the Blue Ribbon Study Panel on Biodefense at the Hudson Institute in Washington, D.C. Her focus was the need to prioritize innovative, nimble, responsive ways for solving existing and new biothreats.

Former HHS Secretary Donna Shalala was commented to the problems of balancing innovation and manufacturing at large capacities:

Sec. Shalala: “It’s one of those fundamental questions of what should government be doing, and when does it profit share. We’re talking about vaccines where the margins are smaller than other drugs.”

DeGroot:“We have also been able to look at existing vaccines and say ‘Wait a minute, we don’t think this is a good idea’. There should be a place for us to say that where it’s going to be heard. And really, there’s no one I can talk to. My experience during H1N1 and during H7N9 is that the CDC doesn’t want to hear that. People do not want to hear that the vaccines that the vaccines that they are going to make (are not going to work). The H7N9 vaccine that we have today is the least effective vaccine that’s ever been made… We told you that in 2013 when sequence (of the virus) was published. We published a paper that the virus was a stealth virus, that new vaccines would be ineffective. Less than ten months later, we were proven right.”

C-SPAN2 recorded a stream of the proceedings. Another CEO, Daniel Abdun-Nabi, of Emergent BioSolutions, also testified for the need to find a way to fund small companies like DeGroot’s to be innovative, but offered that “she’s not going to manufacture”. According to a report in American Progress, Emergent BioSolutions received some $1.3 billion from the U.S. government to produce an anthrax vaccine, which cost them only $250 million to manufacture the vaccine doses.

The contrast was between EpiVax’s focus and the focus of Emergent BioSolutions of the Blue Ribbon Panel was stark. EpiVax wants to reduce roadblocks and cost so the overall approach can be safe and effective. They are extremely good at predicting whether specific vaccines will likely be effective on emerging infectious diseases. In some ways, they are way out ahead of the pack. In reality, they are one step behind. By the time the complete their analyses in response to a threat, the big wheel of status quo has already started turning, and their input is seen as a distraction. This does not need to be so, of course. The big wheel could easily absorb a priori checks on the computed fit between antigen and antibodies, given the sequence, as first-step screen for existing vaccines likely to (or not to) work. The panel seemed focused on the status quo; Gov. Ridge discussed how government has “always worked this way” and both he and Sec. Shalala acknowledge the need for some type of reform. They seemed to want somehow to keep the old system in place and add EpiVax’s ideas to the established large-contract process.

After the testimony concluded, while the Blue Ribbon panelists were not aware, a microphone was left open, which captured the conversation former HHS Secretary Donna Shalala and Gov. Tom Ridge.

Secretary Shalala:”He (Daniel Abdun-Nabi) is making a fortune over there (at Emergent BioSolutions CEO). He’s figured out how to do it. She has not figured out a way to do that yet.”

Gov. Ridge: “That was my take-away exactly.”

Whatever profit model is in play that would transform $250 million investment into over $1 billion profit seems par for the course. For others, such outcomes appear to be a necessary evil, but this is partly because we lack an obvious alternative means by which corporations can bring effective products forward. As health care costs skyrocket, and Americans are asked to pay for their mandatory healthcare insurance or face a fee, one wonders how the Ebola crisis might have been handled if even ½ of those $1 billion went into the development of a vaccine.

The design of clinical trials is a key to success in medical research. As dry as that topic may be, it also part of the answer to why so few drugs are available to us. It is how medical research is done. Thus, the public should learn some details of how clinical trials are conducted. They should also learn of the limitations that are inherent to clinical trials, and find out whether alternatives to the gold standard might improve rates of discovery and translation, and if so, how. I, and many of my colleagues in research, would like to know that we are treated with options that are considered to be most effective, and safe, for each individual patient. There is, therefore, a movement afoot toward ‘personalized medicine’, which attempts to secure, based on information gleaned from individual patients, the best possible clinical route for that patient. Personalized medicine in juxtaposed as an alternative to population-based medicine, and yet the entire biomedical research paradigm is centered on population science. Seeing the tree for the forest can be challenging. But individualized medicine is a key to the success of the effective treatment of many of our most deadly diseases.

There are thousands of promising pharmaceutical compounds on the shelves at pharmaceutical companies. These are known as “orphan drugs”, and they exist at a loss for companies. In fact, they are often pointed to as justification for the high cost of successful drugs. The argument goes like this: For every drug that actually makes it to market, there are a large number of other drugs that do not; we need to recoup the cost of those investments, too”. While it is certainly true that pharma spends billions on R&D, they also spend billions on salaries and bonuses for executives. Also, it is not altogether clear that companies who experience losses due to poor or ineffective exploratory R&D are entitled to recoup their losses. Imagine an ice cream business stating that their high prices were due to all of the flavors they tried out while developing their blockbuster flavors. The difference is the presumed added value in doing failed research because it could have benefited humanity. However, exactly how much of this failed effort is due to poor practices, or inefficiencies that result profit-taking instead of re-investment, is unknown.

Another complicating factor is a trend toward homogenization of healthcare options. While the capitalist in me appreciates an honestly earned financial incentive just like anyone else, there seems to be a missing financial mechanism that uses consumer demand; consumers are often not free to choose directly (they are rarely told all of the options), and this places the medical community as an arbiter in the economic cycle. On top of that sits a regulatory body that by its very nature restricts treatment options, and has moved aggressively to restrict health claims for food products, even when studies strongly support those health claims.

While idealists call for collaborative medical research on tough problems, there is a paradox of translation. The more valuable a new approach to medicine is, the more likely a research institution is to keep it a secret. This means that fewer people around the world can study the problem, and increase knowledge. The more ubiquitous a technique or new drug is, the less valuable it is to a single corporate entity, and while many more people can study it, the less likely it is to be brought forward as a product. Further, as research is a massively parallelized endeavor, it seems likely that some parts of a solution to a medical issue may be known and owned by one entity, while another critical part may be known by others. I have been told by CEOs of some companies that these parts of knowledge often cannot be brought together thanks to the network of lawyers who protect their companies’ intellectual property.

At the height of the Great Recession, I proposed an Intellectual Property Share Market (Lyons-Weiler, 2009) to allow investors to drive forward good ideas in biomedicine and other areas allowing the dollars to vote for the IP that might be brought forward. This idea exists in a less formal way via crowdsource funding; however that approach lacks the financial payoff to investors, as crowdsource funding is usually a gift.

Some point out the fact that people can live with HIV as evidence of success at the level of the FDA, specifically in terms of being able to expedite turn-around times on treatments. However, given that so much is known about the biology of HIV, and that it remains endemic in the human population, AIDS due to HIV infection can hardly be called a translational success. In 2015, estimates are the 1/8 people who are infected with HIV do not know they are infected. Approximate 1 in 4 new HIV infections are in youth aged 13-24, and most of them are not aware of their infection, and that they can pass it on to uninfected persons. Between 1.5-1.9 million people die every year from HIV/AIDS. Over 39 million people have died from HIV/AIDS since the transfer to humans occurred. While the number of deaths due to HIV/AIDS is decreasing, the number of new infections in 2013 was 2.3 million. Overall, there have been 75 million infections worldwide, with around 35 million deaths thus far. That’s a kill rate of around 46%. There are currently around 6,300 new infections per day.

How can the US government agency responses be lauded as a ‘success’? Where is the vaccine? Where is the cure?

HIV is now highly profitable for the pharmaceutical industry, as it produces patients that require lifelong treatment. And yet with a kill rate that rivals those of the deadly Ebolavirus disease, HIV/AIDS is accepted by the public as a fact of life. While we all hope for a cure, the fact is, the disease is endemic to our species, until further notice of cure.

Is this necessary? Or is there a cure, and the HIV drugs more profitable? This type of conspiracy thinking occurs, in large part due to the lack of leadership. Key individuals in positions could have, for example, protested against the US’s solitary negative vote in 2003 against a United Nations resolution on access to drugs in global epidemics such as HIV/AIDS, tuberculosis and malaria. The resolution would have made low-cost, generic versions of drugs available worldwide. When one realizes that the massive profits of the pharmaceutical companies make from treating HIV/AIDS in developed countries comes at a cost of lives in less developed countries, it is easy to see why some proportion of people find those profits ill-gotten. In matters of public health, profit should come as a secondary, not a primary consideration.

Cost effective analysis is usually conducted from an institutions’ point of view, and includes consideration of the cost of adopting a new drug relative to the cost of existing practice, compared to the increase is clinical effectiveness upon adoption of the new drug, i.e,

CE = (C1-C0)/(E1-E0)

This conceptual analysis is made challenging due to the different units (effectiveness must be monetized to appear in the same units (dollars) as cost) and this make analysis not at all straightforward. Profit models nearly always result in the determination of charging what the market will bear. There are some circumstances, at a fixed production cost, in which the increase in the number of units sold due to lowering prices is a major factor in clinical adoption. The larger the percentage of the clinical population that can afford a treatment, the more widespread its use may be. Thus, price models of drugs (which is something that pharmaceutical companies rarely share) may have two or more optimal price points when price can make adoption less likely. Classic break-even analysis does not apply in these situations, because if no one in a clinical population opts for a new treatment due to cost, no price will allow cost recovery.

Not all profits from disease share moral equivalence. Profits gleaned from the prevention of the spread of the disease seem morally sound. Take, for example the case of HIV/AIDs. The FDA approved, in July 2012, the drug Truvada (Gilead, Inc.), which reduces HIV infections in people at high risk of HIV infection when used in combination with condoms and counseling (Grant et al., 2010). Truvada, a fixed-dose combination of Tenofovir/emtricitabine, has minimal side effects. Truvada is not indicated for general use; and HIV/AIDS is on the rise in the poorest parts of the world. Whether cheap generic versions of Truvada may be made available to people with HIV positive partners less developed countries or not remains to be seen. A vaccine or HIV/AIDs always seems to be just around the corner; I hope that research using Virus-Like Particles (VLP’s), such as those used in the Ebola outbreak to screen thousands of potentially effective approved drugs (Kouznetsova et al., 2014) may provide carriers of multivalent vaccination against all major clades of HIV strains. I explore the translational successes of HIV/AIDS more in a chapter in this book.

As ugly as the truth about the preference of profits over treatment options exposed by HIV/AIDS may appear, it would be terribly naïve and great disservice to my biomedical and pharma executive colleagues to represent their mindset considering economic dimensions alone. They, and insurance companies, and healthcare consumers are stakeholders with very distinct – and often contrasting – perspectives and interests. Many prefer to think also in terms of benefits and utility to society. Measures such as quality of life years (QALY) are often considered, and are occasionally monetized for inclusion in cost models. Some models are fairly sophisticated, using statistical resampling methods and Monte Carlo simulations. Nevertheless, the definition of QALY still contains a high degree of subjectivity. However, the concept allows the consideration of the valuation of the clinical benefits of the cost of new treatments compared to existing treatments. A common method is Incremental Cost-Effectiveness Ratio (ICER). Bang and Zhao (2012) advocate for using of the median, not the mean, in ICER analysis due in part to the potential for highly skewed distributions when the care of a few patients in very high. They have also worked out median-based ICER for use with censored data (Bang and Zhao, 2015).

Total costs and total benefits within a given area of clinical practice would capture the entire distribution for an institution, however, and there is no reason not to consider them. From an institutional point of view, and from a producers’ point of view, few factor in the lost income and loss of benefit due to non-adoption caused by price (declined treatments), and therefore cost effectiveness considerations need updating to consider expected partial adoption in the consideration of relative gain.

Price gouging takes place when the seller can place any price, knowing the buyer will pay – or at least try to pay – any price for the product. There are approximately 2.6 million hepatitis C patients in the US. Imagine a drug that could cure hepatitis C – nearly any price above production cost would be a blockbuster and generate remarkable amount of income for the company that produced the treatment. Imagine a company that priced that drug to the point where a mere 30,000 patients and their insurers could afford the treatment in the first year. At high enough prices, even 30,000 patients makes the drug a money-maker, and on the books, projections are that at least that many if not more cases among the wealthy are expected. Thus, massive profits are expected, and the disease will continue to flourish among the (relatively) poor, generating sufficient numbers of paying patient to keep those profits coming.

Express Scripts (2015) produced a report that summarized the trend succinctly, identifying compounded therapies, hepatitis C and cancer medications as the major drivers of increases in health care costs in the US. In 2014, these three types of treatments made up two-thirds of pharmaceutical drug spending in patients whose care cost exceeded $100,000 in 2014. This is due in part to the number of receiving medication treatment for hepatitis C jumped 733% in 2014. Many had delayed other treatment, waiting for a breakthrough. The trends involved increase is use and cost.

Gilead Sciences acquired and manufactures and sells a drug called Harvoni, which completely cures most people with the most prevalent hepatitis C subtype. A three-month costs $94,500, over $1,000 a pill. According to a Bloomberg report, that is more than double the expected cost for the treatment when Gilead acquired the drug from another company (at a reported cost of $11 billion). The drug generated over $10 billion in sales in 2014; thus, Gilead has by now (June 2015) easily recouped the cost of the investment. There are alternatives to Gilead’s one pill per day treatment that are nearly as effective, and insurers are recommending those options to patients.

All of these formal considerations of price and value assessment would be nice if there were evidence that these factors actually are considered in setting a price for new drugs. In an analysis of 51 cancer drugs approved over 5 years, In June 2015, Mailankody and Prasad (2015) of the NIH’s Medical Oncology Service, National Cancer Institute found that the average cost of new drugs was over $100,000. They failed to find any difference in the cost of drugs approved on the basis of progression free survival and overall survival; they found no difference between new drugs with a novel mechanism of action and next-in-line drugs. In fact, there was no discernable relation between the overall improvement in endpoints and cost. The authors concluded that Pharma set the cost at “what the market would bear”.

The tendency to price medicines based on what the market will bear has place many treatments out of the reach of the masses, and causes payees – including Medicare and insurance companies – to refuse treatments based on cost. This leads to lower than possible consumption, and also to artificially-justified inflated prices for similar, even pre-existing options, spiraling health care costs – and profits – into the stratosphere. Competition is supposed to keep prices down. In the case of effective treatments, however, Pharma seems to believe that patients will pay nearly any price. As long as competitors raise prices to maintain projected revenues for investors, the practice will continue until some unseen ceiling it hit. The practice has increase the cost of treatment of multiple sclerosis from about $10,000 a year in the 1990s to over $50,000 a year or higher (Hartung et al., 2015).

The copays add significant financial burden to patients. All of the major drug companies have patient assistance programs that help cover the cost of medication when patients have insufficient insurance, or no coverage and cannot otherwise afford it. However, the cost to government-insured, especially those with fixed annual budgets, means refusal of coverage to other patients, placing effective treatments out of reach for many doctors and patients.

Insurers have long complained about the skyrocketing costs of treatments, and doctors are joining in. The study by Hartung et al. (2015) was motivated in part by the inability of doctor co-authors to provide treatments to their patients.

This practice is anti-capitalist, inhumane, and unsustainable. Bloomberg Business (Tozzi, 2015) called these market trends “Bizarro”, providing an analogy of the first iPhone being manufactured and sold alongside its newer versions at ever increasing prices. The percent increase in the cost of drugs was compiled for Table A1.

DRUG DATE APPROVED INITIAL COST(IN 2013 DOLLARS) 2013 COST INCREASE
Interferon-β-1b (Betaseron) 7/23/1993 $18,591 $61,529 231.00%
Interferon-β-1a IM (Avonex) 5/17/1996 $12,951 $62,394 381.80%
Glatiramer acetate (Copaxone) 12/20/1996 $12,312 $59,158 380.50%
Interferon-β-1a SC (Rebif) 3/7/2002 $19,763 $66,394 236.00%
Natalizumab (Tysabri) 11/23/2004 $31,879 $64,233 101.50%
Interferon-β-1b (Extavia) 8/14/2009 $35,644 $51,427 44.30%
Fingolimod (Gilenya) 9/21/2010 $54,245 $63,806 17.60%
Teriflunomide (Aubagio) 9/12/2012 $48,349 $57,553 19.00%
Dimethyl fumarate (Tecfidera) 3/27/2013 $57,816 $63,315 9.50%
Notes        
All costs are annual.        
2013 costs were sampled in December of that year.    
Interferon-β-1b is marketed as Betaseron by Bayer and Extavia by Novartis.  
Source:Hartung et al., 2015      
         

The prices for these drugs are about ½ those in Table A1 in Canada, Australia, and the UK (Hartung et al., 2015). These patterns reflect a trend not restricted to MS drugs.

The tendency for old, competing drugs to be priced higher due to overpricing by that latest approved drug is bizarre; it is hard to understand from standard supply-side driven competitive market dynamics.

Under normative free market supply and demand dynamics, producers will provide increased supply as prices rise because all firms will look to maximize profits. Under this model, supply is a function of price and quantity. A positive correlation usually exists between price and quantity. Typically, demand increases when prices are low, consumers tend to purchase a larger quantity of the product. When prices are high, consumers tend to purchase a lower quantity. Supply and demand influence each other differently depending on availability of the product – that is, it is usually seen that producers control the specific conditions that drive supply, and therefore, demand. Surpluses and shortages due to changes in production cause fluctuation until the product reaches a fair market value.

There are myriad oddities about pharmaceutical economics (pharma economics) that do not fit this typical model. Factors that increase demand (in addition to decreased prices due to surplus and competition) include increased incidence of disease, greater consumer awareness, and advocacy for purchase via clinicians. Direct-to-consumer marketing can increase demand for a specific treatment. DTC marketing tends to make consumers believe that the drug being advertised is as the latest-breaking treatment, and they assume that it is also the most effective. Neither of these assumptions are safe assumptions, and thus patients rely heavily on the advice of their doctors.

In market force economics, price is usually negatively responsive to competition. In pharma economics, this dynamic is missing because producers of older options find that the average market value of treatments same in class increases. The result is a positive feedback loop with negative consequences: Price increases become a runaway process, leaving some consumers out. A main difference here is that in medicine, consumers may be left out of the selection of offerings on the market by many intermediary stakeholders.

In pharma economics, individual patients do not consume more than the prescription requires; theirs is a fixed consumption schedule, and, for many conditions, for a short duration. The demand curve is not only flat, as some have decried. In normal market economics, a flat demand curve makes it difficult for producers to effectively vary their production output in a manner that allows them to take advantage of the principles of supply and demand. This usually drives innovation.

In pharma economics, the flat (but steady) demand curve is of little significance because the majority of consumers have less control over their consumption decisions. It is as if the market for some drugs are stuck on a single point of demand (high) when in fact, demand is inflated by the existence of payors other than the consumer: Medicare, Medicaid, insurance companies, and event the producers will pay into the cost of the medicine for a patient as a free subsidy of their entire copay.

When the drugs are life-saving, this comes across to the public as philothropy. A pure cynic would view this strategy as a shrewd investment with a handsome profit and a PR boost. After all, copays are often a mere fraction of the total price of a drug, and the cost of product is much lower than the price. Thus, the idea goes, pharmaceutical companies manipulate both the supply and demand side of the market, driving the runaway price increases.

Some in business will see this as an ultimate expression of free market capitalism, and will celebrate pharma’s successes unapologetically.

Others (mostly consumers) will see this as a perversion of free market capitalism; they will feel manipulated, and they will experience a sort of buyer’s regret, for not having received a better deal – not knowing the details of the imagined better deal. They will know that they (as a class) will have been bilked somehow, in some way (perhaps via higher insurance premiums, or higher overall copays).

Even when some patients are left out due to cost, the fact that some consumers cannot afford the treatments is irrelevant because the loss in potential profit from those consumers is hidden by the artificial increase in drug prices. This inflation is boon for everyone except low-income consumers.

This outcome is similar to a phenomenon in market science in which one producer is strong and is faced with weak competitors; providers facing weak competition are likely to apply high mark-ups and set prices above the competitive level.

This unhooking of the relationship between supply and demand replaces the free market with an economic oligarchy. The process is not identical to price fixing, because companies that are competing are not communicating with each other directly. They pay less attention to the normative factors that cause them to set a price (units sold) and more attention to the price range of similar options for healthcare, even when those options are not same-in-class. The competitors are, however, communicating with each other via their pricing.

Society objects to exorbitant profits when it means that the price will place the product out of reach of some of the patients. However, when society values a product to the extent that our society values drugs that either save our lives or dramatically improve or maintain our quality of life, the potential for market-independent pricing is high.

Such an outcome can have dire consequences, especially in terms of limited supply for deadly infectious diseases and in seasonally fluctuating diseases. These factors conspired to lead to a serious shortage of availability of effective malaria drugs in Cambodia (Patouillard et al., 2015).

In the US, key voices have described pricing as “chaotic”, citing immense and unpredictable pricing from provider to provide, and high regional variation (Shanley, 2011).

In a large market where company value is measured in terms of stock values (which are in principle determined by dividends) the pressure to stay competitive is immense. At some point, the absolute value of a product loses meaning, and the relative value becomes paramount. That is, the dollar value of your product only makes sense in terms of the value of your competitor’s product because as they stand to profit more than you, the value of their company stands to increase faster than yours. They stand to benefit at a compounded rate, and thus will be able to outcompete you directly on the product in question, but also in other areas of competition (better investment in R&D, more marketing, etc.). Thus, to stay relevant, the pressure to keep your price up with others is immense: Prices begin to drift higher and higher away from commodity value as each company checks the value of their offerings against the market.

The resulting runaway increase in pricing brings to mind the statement by the Red Queen to Alice in Lewis Carroll’s “Through the Looking Glass”:

“Now, here, you see, it takes all the running you can do, to keep in the same place”.

Go/No Go decisions also influence the scope of health care options. Such was the case for vaccine development in Ebola. The pharmaceutical company’s profit filter is one of many that determine which options for care are even available to our doctors. But it is not the only factor. At question is not whether doctors are willing to treat patients, or cure them. The action of choosing a particular route of medical care is often a result of consultations with peers, dependent on protocols, approved by associations, limited by the FDA regulatory process and dependent on approval by health care insurance providers. Sometimes, small changes in healthcare practices are so easy, practical, and inexpensive, that it makes one wonder why all improvements don’t come that easy. An example of this kind of translation is the observation by one doctor that patients who were acquiring pneumonia infections after surgery and dying while being treated for other diseases needed to have the head of their beds raised. Patients at risk of developing pneumonia are now also advised to breathe deeply and cough 4-5 times an hour to prevent the illness – a no-cost, life-saving practice that can never be put on the stock market.

Health care spending on prescription medications accounts for1.6% of gross domestic product in the United States (Centers for Medicare and Medicaid, 2014). The use of, and constantly increase in the price of brand-name prescription medications is the primary driver of this growth, increasing 15% in price in 2014 alone (Silverman, 2015).

Use of comparatively lower priced generic drugs now accounts for 86% of all prescriptions. Generics have saved US consumers nearly $1.5 trillion in the past decade (GPHA Online, 2014).

One might suspect that some doctors may offer name-brand drugs over less expensive generics; to a degree, those suspicions are correct. Patients are evidently complicit in this; Campbell et al. found that patient demand for name-brand drugs is one factor that in part explains why doctors tend to prescribe more expensive name-brand options over generics. Other factors include type of doctor, and years of clinical experience: Older doctors were more likely to acquiesce to patient requests for name-brand drugs (Campbell et al., 2013). Some doctors may write (“Dispense as Written”, or check a box, which then mandates that the pharmacist use only name-brand versions of a drug. They do so at the risk that some patients will be less likely to use the medication as directed: They may skip doses, to extend the time between filling expensive scripts, leading to less efficacy. Patients receiving less expensive generics showed a 12% increase in compliance (Shrank et al., 2006).

To stem the rising tide in cost, substitution laws have been passed in every state. These laws either authorize or mandate pharmacists to fill most prescriptions for a brand-name drug with its generic counterpart. Similarly, tiered insurance formularies are used to impose higher cost-sharing obligations on patients for brand-name drug. Paying clinicians to prescribe generics legal for some, but not all payors (Sarpatwari et al., 2015).

With all of the regulatory hurdles, and the profit pressures, sometimes, it seems a wonder that any improvements in medicine occur at all. In this book, I explore the pitfalls of modern medical research and point to instances that seem to confirm that American public’s suspicion of cure vs. treatment decisions. I also try to provide a balanced view, by interviewing experts on specific topics, and highlight where more information via research is needed. A book on those topics alone would do nothing more than stir discontentment and suspicion. I use this book also as an opportunity to explore the many successes in a type of medical research called translational research. As I researched each topic, and dove deep into the published records of scientific publications, articles, prospectuses from corporations, and interviews with the researchers behind the translational successes, my journey was open-ended. However, I sought to identify the key characteristics of the researchers, the medical problems, and the research studies themselves that contributed to their translational successes.

References

Bang H, H Zhao. 2012. Median-based incremental cost-effectiveness ratio (ICER). J Stat Theory Pract. 6(3):428-442.

Bang H, H Zhao. 2015. Median-based incremental cost-effectiveness ratios with censored data. J Biopharm Stat. http://dx.doi.org/10.1080/10543406.2015.1052482.

Campbell EG et al., 2013. Physician acquiescence to patient demands for brand-name drugs: results of a national survey of physicians. JAMA Intern Med. 173(3):237-9. doi: 10.1001/jamainternmed.2013.1539.

Centers for Medicare and Medicaid. 2014. NHE Factsheet. http://www.cms.gov/Research-Statistics-Data-and-Systems/Statistics-Trends-and-Reports/%20NationalHealthExpendData/NHE-Fact-Sheet.html.

Express Scripts, 2015. Super spending: US trends in high-cost medication use. http://lab.express-scripts.com/insights/drug-options/super-spending-us-trends-in-high-cost-medication-use

GPHA Online (Generic Pharmaceutical Association & IMS Institute for Healthcare Informatics). 2013. Generic drug savings in the U.S. http://www.gphaonline.org/media/cms/%20GPhA_Generic_Cost_Savings_2014_IMS_presentation.pdf.

Grant RM et al. 2010. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 363(27):2587-2599.

Guest J, Dietrich WD. 2015. Commentary regarding the recent publication by Tabakow et al., “Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging”.J Neurotrauma. 2015 Mar 31. [Epub ahead of print]

Hartung DM et al. 2015. The cost of multiple sclerosis drugs in the US and the pharmaceutical industry: Too big to fail? Neurology. 84(21):2185-92. doi: 10.1212/WNL.0000000000001608.

Kouznetsova J et al. 2014 Identification of 53 compounds that block Ebola virus-like particle entry via a repurposing screen of approved drugs. Emerging Microbes and Infections 3: e84. doi:10.1038/emi.2014.88

Lyons-Weiler, J. 2009. Time for an IP Share Market? The Scientist. To view online: http://www.the-scientist.com/?articles.view/articleNo/27084/title/Time-for-an-IP-Share-Market-/

Mailankody, S and V Prasad. 2015. Five years of cancer drug approvals innovation, efficacy, and costs. JAMA Oncology, Published online April 2 2015, doi:10.1001/jamaoncol.2015.0373. http://oncology.jamanetwork.com/article.aspx?articleid=2212206

Patouillard E. 2015. Determinants of price setting decisions on anti-malarial drugs at retail shops in Cambodia. .Malar J. 14:224. doi: 10.1186/s12936-015-0737-9.

Perkowski, J. 2014. Health care: a trillion dollar industry in the making. Forbes Magazine 11/12/2014. http:www.forbes.com/sites/jackperkowski/2014/11/12/health-care-a-trillion-dollar-industry-in-the-making

Sarpatwari A et al., 2015.Paying physicians to prescribe generic drugs and follow-on biologics in the United States. PLoS Med. 12(3):e1001802. doi: 10.1371/journal.pmed.1001802.

Shanley, A. 2011. From the Editor: Drug prices? Eenie meenie miney mo. Pharmaceutical Manufacturing. http://www.pharmamanufacturing.com/articles/2011/091/

Shrank WH, et al. 2006. The implications of choice: prescribing generic or preferred pharmaceuticals improves medication adherence for chronic conditions. Arch Intern Med 166: 332–337.

Silverman E. 2015. Prices for prescription medicines rose how much last year? http://blogs.wsj.com/pharmalot/2015/01/26/prices-for-prescription-medicines-rose-how-much-last-year/.

Tabakow P et al., 2014. Functional regeneration of supraspinal connections in a patient with transected spinal cord following transplantation of bulbar olfactory ensheathing cells with peripheral nerve bridging. Cell Transplant. 23(12):1631-55. doi: 10.3727/096368914X685131.

Tozzi, J. 2015. How much would you pay for an old drug? If you have MS, a fortune. Bloomberg Business, April 25, 2015.

causes

 

Dear American Press: Enough with the Rhetoric. Tell the Full Autism/Vaccine Safety Research Story

PRESIDENTIAL HOPEFULS on the GOP ticket touched a bit of a third rail in the debates on Wednesday night.JLW1

The ANTI-VACCINE SAFETY PRESS (how do you like it?) ran into overdrive to perform damage control on their favorite, most-run story on vaccines and autism: that, again, for (sigh, when will people ever understand, I suffer so!) the BILLIONTH time, “Vaccines Do Not Cause Autism”. They are no doubt trying to save countless lives by teaching people that vaccines save lives.

In support of their positions, each story used well-worn tactics of argumentation. They cited “dozens” of studies that have been published.

Where is the Fourth Estate?

The Washington Post went back in time to 1998 to the Wakefield affair.

But The Post they did not go back to August, 2014 to the news that Dr. William Thompson confessed that the CDC fudged data on vaccine safety, nor did they mention Thompson’s statement via his lawyer’s website that verified that yes, they omitted results. And that he regretted doing harm to people.

The Post also cited the 2004 by the National Academy of Sciences/Institute of Medicine review that concluded that “the evidence favors rejection of a causal relationship between thimerosal-containing vaccines and autism.”

Oddly, they neglected to reference the updated (2012) National Academy of Science/IOM report that rejected 17/22 studies that had been touted as “evidence” that autism is not linked to vaccines.

The New York Times went so far as to tell the candidates (and the American public) that vaccines are “not up for debate”.

Excuse me?

Since when does a news organization, which is supposed to objectively report the news, determine the issues that are “open to debate”? They should go back to reporting, and not creating, the news.

The same article cited the outlandish (and irresponsible) statement by Dr. Paul Offit that vaccines are so safe that they could tolerate 100,000 shots at the same time. Really?

Is that rational debate? Each 100,000 shots of just about ANYTHING would likely kill any child. They are not even taking safety seriously. At all.

I take it seriously. Here is the text from the NAS/IOM 2012 report:

The committee reviewed 22 studies to evaluate the risk of autism after the administration of MMR vaccine. Twelve studies (Chen et al., 2004; Dales et al., 2001; Fombonne and Chakrabarti, 2001; Fombonne et al., 2006; Geier and Geier, 2004; Honda et al., 2005; Kaye et al., 2001; Makela et al., 2002; Mrozek-Budzyn and Kieltyka, 2008; Steffenburg et al., 2003; Takahashi et al., 2001, 2003) were not considered in the weight of epidemiologic evidence because they provided data from a passive surveillance system lacking an unvaccinated comparison population or an ecological comparison study lacking individual-level data. Five controlled studies (DeStefano et al., 2004; Richler et al., 2006; Schultz et al., 2008; Taylor et al., 2002; Uchiyama et al., 2007) had very serious methodological limitations that precluded their inclusion in this assessment. Taylor et al. (2002) inadequately described the data analysis used to compare autism compounded by serious bowel problems or regression (cases) with autism free of such problems (controls). DeStefano et al. (2004) and Uchiyama et al. (2007) did not provide sufficient data on whether autism onset or diagnosis preceded or followed MMR vaccination. The study by Richler et al. (2006) had the potential for recall bias since the age at autism onset was determined using parental interviews, and their data analysis appeared to ignore pair-matching of cases and controls, which could have biased their findings toward the null. Schultz et al. (2008) conducted an Internet-based case-control study and excluded many participants due to missing survey data, which increased the potential for selection and information bias. The five remaining controlled studies (Farrington et al., 2001; Madsen et al., 2002; Mrozek-Budzyn et al., 2010; Smeeth et al., 2004; Taylor et al., 1999) contributed to the weight of epidemiologic evidence and are described below.

What’s that? DeStefano et al., (2004) – one of the very studies that Thompson reported that he and colleagues had strong preliminary association results in co-morbid free autism cases, and in African American males – both results which were omitted from the study.

Yahoo! Health tapped an expert in Infectious disease, who claimed that sudden onset of autism is an “odd statement”:

“It’s an odd statement because the diagnosis of autism is made over months and years, not right after a child has a fever,” he says. “It’s a behavioral neurological disorder.”

That expert, Dr. Martin Hirsch, MD, professor of medicine at Harvard Medical School and a senior physician in the Infectious Disease Unit at Massachusetts General Hospital, might have done well also to read the 2012 IOM report:

Because the timing of diagnosis or recognition of autism coincides with
the administration of many vaccines, questions have been raised regarding potential etiologic relationship(s) between the two. There are several challenges in interpreting existing data. Establishing a temporal relationship
between a potential inciting event (such as vaccine administration) and
the onset of autism is difficult because dating the onset of the syndrome in most cases is imprecise (although there is a subset of children with acute regression from reportedly normal development). Rechallenge data are not available, since most children do not rapidly (if ever) recover a normal developmental pattern following the onset of their symptoms.

Perhaps Dr. Hirsch should have consulted case reports, such as that of Hannah Poling, who, after receiving vaccinations on July 19, 2000, regressed within a few days into classic and severe infantile autism (Oller and Oller, 2010). Hanah’s case is consider ‘typical’ of regressive autism.

Regressive autism used to be rarer than natal autism; however, these news outlets failed to report that over the time period that the vaccine schedule was expanded, the percentage of total cases of autism that were of the regressive form increased:

“By 1985 the incidence of regressive autism had equalled that from birth. By 1997 both types had increased although the regressive form was now >75% of the total occurrence. This suggests that an acquired condition was overtaking birth defects or purely genetic conditions.” (Ewing, 2009).

News outlets need to stop playing bait-and-switch on the issue of vaccine safety and do their job. When someone brings up questions about the validity of vaccine safety research, they go right to efficacy. Those questioning safety are chastised and minimized. Check out the post’s “news” article – (they puts quotes around the word ‘debate’, so I put quotes around ‘news’):

The GOP’s dangerous ‘debate’ on vaccines and autism.

It is abjectly ridiculous to think that Americans should not discuss or learn about vaccine safety. Or the lack thereof. And it is intolerable for the American Press to ignore one of the largest stories in the history of medicine in the US, and perhaps in the history of the world.

Yahoo! Health’s focus is on the “horror” of doctors. Take the excerpt:

““These politicians are making everybody anxious about an issue and then potentially harming the general population,” Lawrence Michael Dell, MD, primary care specialist at Internal Medicine & Primary Care Specialists in West Bloomfield, Mich., tells Yahoo Health. “If the average American doesn’t look into the efficacy of vaccines, they may say ‘I’m not going to vaccinate my child’ based on these comments.”

No, Dr. Dell, we were not discussing efficacy. That’s not the discussion the we were having. Let’s try this re-focus back on safety:

“When the average American looks into the sorry state of vaccine safety research, they may say ‘I’m not going to vaccinate my child’ based on the reports that the research was reported to be fraudulent by a senior scientist at the CDC.”

Now there’s a focused discussion point.

Concerns over safety cannot be effectively addressed by brow-beating the American public with efficacy.

It is highly irrational for anyone to change the topic from safety to efficacy. Imagine someone who was exceptionally good at walking a tight-rope who became so enamored with their high skill level who decided that they no longer needed a safety net. Is that a reasonable thing to do? They can be good at walking a tight-rope, AND have a safety net. Just in case.

Or imagine car seats that were observed, by some percentage of parents, to give children permanent brain damage. There would be an uproar. To counter with “But car seats save lives!” would convince very few people that the design flaw in the car seats should not be fixed.

We are told that if we only understood the utility function properly that the adverse events associated with pediatric vaccines, then we would see that the suffering of the small percentage of kids who might undergo serious, debilitating reactions are worth it. Really?

What percentage of children should the American people tolerate receiving permanent brain injuries due to car seat manufacturing flaws?

“But car seats save lives!  So don’t talk about their safety, it’s not up for debate.”

Yes, ok. That’s not going to happen.

Vaccines, like car seats, are manufactured. They are man-made. The risks that we are asked to endure for our children in terms of adverse events may be rare, but they are not trivial. Because they are man-made, they can be changed. Improved. Updated. Made more safe.

Or, at least we should look into why some people have adverse reactions, and some do not. In any other medical research setting, the public would be hearing about, with fanfare heralding a new era of medical science:

Individualized medicine. Biomarkers. Big Data.

As the pharmamedia projects to the public the perspective that there is no need to concern ourselves with the safety of vaccines, we’re left with the sense that no vaccine safety research need ever be conducted again. After all, vaccines save lives, right?

The discussion is not on whether vaccines save lives. We all know that they do. The discussion is whether they harm people, and whether the research conducted to date is reliable, and whether the CDC committed scientific misconduct, fraud, and whether they continue to mislead the American public on the accuracy of Dr. Thompson’s revelations of same?

I would not be involved in this ‘debate’ were it not for the egregious handling of public education by the CDC on Ebola. When Direct Tom Frieden testified there were no mutations in the virus to the House Select Committee hearings, I was so moved by the attendant risks of that level of ignorance, or misinformation, about a disease so deadly, that I wrote a book to help set the record straight. Medical practitioners, including nurses, need accurate information to know how to care for Ebola patients. They also need to know the reality of the risks they ask their patients to endure when they vaccinate them.

The CDC markedly and repeatedly assured us that we are all going to be OK, even with an outbreak of a disease as deadly as Ebola in the US, due to our advanced medical infrastructure (that claim, by the way, is almost certainly false. Ten cases in one city would exhaust the resources available for handling the infectious liquid waste). And yet we told that anyone questioning vaccine safety is risking, it would seem, the entire population of the US with certain death – just by holding discussions on what we really, truly know about whether vaccines are safe?

I would also not be involved in this topic were it not for Dr. William Thompson’s confessions. He did not merely allege that OTHERS at the CDC fudged and omitted data in numerous studies; he stepped forward to say that he himself participated in these activities. The man was risking, for all he knew, jail time and fines for defrauding the American government of research funds.

So, by all means, let’s sweep the New York Times aside, and let’s continue the debate.

In the Yahoo! Health article,  Dr. Danelle Fisher, MD, vice chair of pediatrics at Providence Saint John’s Health Center in Santa Monica, Calif., says there is a “huge amount of medical evidence” that supports the safety of the vaccine schedule, published by the Advisory Committee on Immunization Practices in conjunction with the American Academy of Pediatrics and the Centers for Disease Control and Prevention.

And then, she follows with the chronic non-sequitur statement:

“The vaccine schedule is there for a reason.”

Really. Vaccines exist for a reason. Well thank you, Dr. Obvious!

The American Press also does not report on financial conflicts of interest among members of the Advisory Committee on Immunization Practices.  Well, CBS News did run an article on this issue. Back in 2008. Fourteen Studies did an excellent job reporting on these organizations:

  1. The American Academy of Pediatrics The American Academy of Pediatrics, a private, non-profit organization, is perhaps one of the few organizations powerful enough to put and end to the autism epidemic. Ostensibly, their focus should be the health of American children. Instead, the interests of the vaccine program and pharmaceutical companies always seems to come first. Here’s a great article from CBS Evening News: How Independent Are Vaccine Defenders?Among the many sins the AAP has committed:
    • Of the 19 actual studies we critique on this website, 50% were published in Pediatrics, the trade journal of the AAP.
    • The AAP has actively lobbied in states to keep mercury in children’s vaccines and against state bans
    • The AAP has yet to acknowledge there is an actual rise in the number of cases of children with autism and instead continues to imply that rising autism levels may solely be due to “better diagnosis”
    • The AAP does not acknowledge, nor have they been known to pursue, any of the hundreds of reported cases of recovery from autism through biomedical intervention
  2. The Advisory Committee on Immunization Practices (ACIP)
    Centers for Disease Control According to the CDC’s website, “the ACIP consists of 15 ‘experts‘ in fields associated with immunization who have been selected by the Secretary of the U. S. Department of Health and Human Services to provide advice and guidance to the Secretary, the Assistant Secretary for Health, and the Centers for Disease Control and Prevention (CDC) on the most effective means to prevent vaccine-preventable diseases.”The ACIP is responsible for expanding the number of required vaccines for children from 10 in 1983 to 36 in 2007 (see a comparison here), without ever ensuring that the schedule was tested in combination or that appropriate monitoring took place for delayed onset conditions.The ACIP was the topic of a document titled Conflicts of Interest in Vaccine Policy Making written by the U.S. Congressional Subcommittee on Government Reform which highlighted the conflicts of interest present between ACIP members and pharmaceutical companies manufacturing vaccines.
  3. Paul Offit, M.D.
    Chief of the Division of Infectious Diseases, Children’s Hospital of Philadelphia Mr. Offit appears to be the pharmaceutical industry’s go to Doctor to speak to the press about the safety of the current vaccine program. He is also the patent holder for the new rotavirus vaccine, recently added to the Immunization Schedule, and a past member of the ACIP (See #1). Among his many outrageous statements, Mr. Offit wrote in the journal of Pediatrics that a child’s immune system could handle 10,000 vaccines:“A more practical way to determine the diversity of the immune response would be to estimate the number of vaccines to which a child could respond at one time…then each infant would have the theoretical capacity to respond to about 10,000 vaccines at any one time.”Regarding Thimerosal in vaccines:“In some instances I think full disclosure can be harmful. Is it safe to say there is zero risk with thimerosal, when it is remotely possible that one child would get sick? Well, since we say that mercury is a neurotoxin, we have to do everything we can to get rid of it. But I would argue that removing thimerosal didn’t make vaccines safer — it only made them perceptibly safer.”On potential conflicts of interest as a vaccine patent-holder:“I am a co-holder of a patent for a (rotavirus) vaccine. If this vaccine were to become a routinely recommended vaccine, I would make money off of that. When I review safety data, am I biased? That answer is really easy: absolutely not.”Speaking to a journalist:

    “You did more harm than good in sort of quote/unquote allowing the parent to be fully informed [regarding the presence of mercury in vaccines]. There’s no politically correct way to say this, but being fully informed is not always the best thing. You can take that out of context and make me look like a jerk, but you know what I’m saying.”‘

It’s not out of context to report a conflict of interest. And the existence of a conflict of interest are not excused by one’s claim that they are not influenced by profit motives. And the American Press stays eerily silent on this side of the issue.

Why do 2015 press articles cite a 2002 IOM review, but not the more recent, updated 2012 review? If these publications include any rejected by the IOM in 2012, then we have not only selective reporting by the Press, but selective citation of the scientific literature. That alone is a form of bias.

The Yahoo! Health article then say that Fisher claims that “it can be potentially dangerous to spread out a vaccination schedule because nearly all of the vaccinations given are not 100 percent effective with the first dose. Spreading out the schedule has ‘no scientific merit,’ she says, and can leave children more susceptible to contracting the diseases you’re trying to protect against until the schedule is complete.”

What she didn’t say is that the effects of wholescale changes to the pediatric schedule that have occurred over the last 15 years have never been studied at all. Instead, vaccines are studied, one at a time, with research funds provided by the manufacturers of vaccines, who, by the way, are completely indemnified from lawsuits for damages or liability for injuries. There are over 250 vaccines in the pipeline – a profiteer’s dream.

The American Press also does not report on the assault on personal liberties that the choice about vaccines embodies. Two words sum it up: Informed Consent.

As for me, I believe that vaccines save lives. I also believe it is a fundamental human right to refuse a particular form of medical care and opt for others. I believe that the CDC has failed to demonstrate the safety of vaccines (re: Dr. William Thompson’s confession of his and others’ scientific misconduct during vaccine safety studies during the 2000’s, which help set the current pediatric schedule. I’ll say it again: I believe vaccines save lives. But informed consent laws required that we are informed with accurate information about the state of knowledge of the safety of the food and drugs we are given.

This is not longer about vaccines. It’s about whether we still have a free and independent press in America. Or do we know live in a Pharmatopia? It’s about whether conflicts of interest still matter. And it’s about whether faked science still matters.

Do we really want to be a country that forces specific medical care upon patients without consent? Consent by coercion is not recognized as consent under any setting. The Universal Code of Human Rights – and the Nuremberg Code – both say that forced medical treatment is unethical. Ask yourself why would anyone want to force this medical, when they also know about the scientific misconduct  – it’s entered into the Congressional Record thanks to Rep. Bill Posey (FL-R).

I’m a demoncrat (that’s a joke, son), and I love Posey for bringing this issue forward. Don’t let them do this with vaccines – what else will they force on us in the name of easily justified profits from mass vaccinations?

We should be overhauling our vaccine safety research programs instead.

Appreciation is extended to my son Zach for the word “Pharmatopia”. I had been using the awkward term “Pharmacocracy”. 

What do you think? Should the press tell the whole story? Or should they just be ‘responsible’ and report in a manner that is designed to get people to adhere to the CDC’s vaccination schedule?  Does a Fourth Estate even exist in this country? Do ethics still matter in vaccine medicine? Feel free to comment. Detractors welcome!

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Further Insights on the Evolution of Ebola: The Molecular Control of Infectivity Hypothesis in Light of New Data

SLOWLY, INEXORABLY, Ebola virions are reproduced in the cell, and pass Evolution_is_Realthrough the cell membrane, ready to infect new cells.

That does not sound like the Ebola we know. Surely Ebola ravages through the body at break-neck speed, devastating cells and tissue and organs as it makes it way through it typical route to the end-stage pathological crisis of coagulopathy.

But new evidence suggests the in the case of Ebola’s fitness, less may be more – and also that some mutations in Ebola may yet to be shown to have had an impact on the degree of virulence by influencing,  as I also proposed was possible in “Ebola: An Evolving Story“- the rate of viral reproduction, which should then determine infectivity.

Readers will recall my missive against the widespread idea that high virulence and pathogenicity of an infectious agent are associated with increased mutation rates.  This idea seems to have originated from the observation that non-synonymous substitution rates may be expected to higher than synonymous rates when positive Darwinian selection is occurring.  Somehow, in the formation of public policy, however, the overall rate itself became a proxy measure of virulence – as if natural selection would act to increase the mutation rate rather than to be reflected by the increase in certain phenotypes encoded by from various genotypes that might emerge from substitutions that have occurred. Is worth pointing out that the least interest nucleotide substitutions nearly always have the highest rate (third positions in codons, introns in animal genomes), and thus the notion of the use of a high mutation rate as a sign of increase virulence or pathogenicity is not warranted based on evolutionary principles.

An alternative hypothesis worth consideration is whether Ebola (or any emerging infectious agent) that comes into the human species via what David Quammen has called “spillovers” adapts to us as a new host via a mechanism that involves, after a series of transmissions, an overall slowing of the rate of disease progression, because virion types (quasispecies) that stick around in a living host longer have a better shot at either being transmitted, or of having descendants that are transmitted, to another member of the same newly colonized species (in this case, Homo sapiens).

While the rest of the world focused on the low probability that Ebola may undergo a shift to become “airborne”, following the plot line of the movie “Outbreak”, the specific mechanisms that I envisioned by which Ebola might slow down, or speed up the disease progression rate included

  • specific nucleotide substitutions that lead to increases or decreases in the rate at which the Ebola genome can be replicated;
  • changes in the rate of the stuttering of the transcription of the GP gene, which leads to the production in sGP, the truncated version of the Ebola GP protein. The sGP protein is thought to be of benefit to Ebola by overwhelming the adaptive immune system with it large numbers;
  • improving in the ability of the virus to undergo asymptomatic, or presymptomatic, transmission;
  • change in the host (human patient) tissue virulence patterns;
  • change in the primary mode of death.

Ebola from Guinea in 2013/2014 may have undergone any, or all of these types of shifts in phenotype.

I am not the first to conceive that specific mutations might also cause shifts in pathogenicity in Ebola.  Take, for instance, this from a study in 2004:

” Likewise, GP shedding may play an important regulatory role in virus replication and pathogenesis” (Dolnik, 2004).

Public policy in the US was based primary on viewpoints from the CDC. I express in “Ebola” how shocked I was to hear Dr. Tom Freiden, Director of the CDC relay to the world, including the entire US medical community, that there we no mutations in Ebola from guinea. I also report my incredulity at the report to the scientific community, during a White House conference call, that Ebola from guinea was “well over 99.999% ” similar to Ebola zaire from 1995 (it’s not – it’s as much as 97.3% similar). The “99.999%” answer came from a CDC Senior Scientist in response to my question about what may, or may not be yet known, about the in the form of a question about the 396 mutations found to date (at the time) in Ebola from guinea.  How many, and which mutations, is an important question for a virus as deadly as Ebola. Why the CDC consistently downplayed even the existence of potentially important mutations is a mystery – it has left much of the scientific community shaking their heads and wondering “Why“?

Studies of molecular phenotype is challenging science. Working with Ebola is even more challenging. So it is remarkable that a research team at Emory University were able to show convincingly that high amounts of the GP1,2 protein actually leads to lowered infectivity.  Here is the abstract from their study (Mohan et al., 2015):

The Ebola virus (EBOV) surface glycoprotein (GP1,2) mediates host cell attachment and fusion and is the primary target for host neutralizing antibodies. Expression of GP1,2 at high levels disrupts normal cell physiology, and EBOV uses an RNA-editing mechanism to regulate expression of the GP gene. In this study, we demonstrate that high levels of GP1,2 expression impair production and release of EBOV virus-like particles (VLPs) as well as infectivity of GP1,2-pseudotyped viruses. We further show that this effect is mediated through two mechanisms. First, high levels of GP1,2 expression reduce synthesis of other proteins needed for virus assembly. Second, viruses containing high levels of GP1,2 are intrinsically less infectious, possibly due to impaired receptor binding or endosomal processing. Importantly, proteolysis can rescue the infectivity of high-GP1,2-containing viruses. Taken together, our findings indicate that GP1,2 expression levels have a profound effect on factors that contribute to virus fitness and that RNA editing may be an important mechanism employed by EBOV to regulate GP1,2 expression in order to optimize virus production and infectivity.

IMPORTANCE The Ebola virus (EBOV), as well as other members of the Filoviridae family, causes severe hemorrhagic fever that is highly lethal, with up to 90% mortality. The EBOV surface glycoprotein (GP1,2) plays important roles in virus infection and pathogenesis, and its expression is tightly regulated by an RNA-editing mechanism during virus replication. Our study demonstrates that the level of GP1,2 expression profoundly affects virus particle production and release and uncovers a new mechanism by which Ebola virus infectivity is regulated by the level of GP1,2 expression. These findings extend our understanding of EBOV infection and replication in adaptation of host environments, which will aid the development of countermeasures against EBOV infection.

A glimmer of light on the possible mechanisms involved in shifts in the rates of ebola virus disease progression in a patient appeared this month in The Journal of Infectious Disease. A study by Dolnik et al., (2015) reported that virions made to have specific mutations had a lower rate of ‘shedding’ out from infected cells than virions with the 1995 genotype [sentence edited 9/12/15]. The mutations in question are not from the Guinea isolates, but were studied based on their previously studied effects on specific pathways likely to influence pathogenicity.

Here’s the abstract from the Dolnik et al., (2015) study:

The surface glycoprotein (GP) is responsible for Ebola virus (EBOV) attachment and membrane fusion during virus entry. Surface expression of highly glycosylated GP causes marked cytotoxicity via masking of a wide range of cellular surface molecules, including integrins. Considerable amounts of surface GP are shed from virus-infected cells in a soluble truncated form by tumor necrosis factor α–converting enzyme. In this study, the role of GP shedding was investigated using a reverse genetics approach by comparing recombinant viruses possessing amino acid substitutions at the GP shedding site. Virus with an L635V substitution showed a substantial decrease in shedding, whereas a D637V substitution resulted in a striking increase in the release of shed GP. Variations in shedding efficacy correlated with observed differences in the amounts of shed GP in the medium, GP present in virus-infected cells, and GP present on virions. An increase in shedding appeared to be associated with a reduction in viral cytotoxicity, and, vice versa, the virus that shed less was more cytotoxic. An increase in shedding also resulted in a reduction in viral infectivity, whereas a decrease in shedding efficacy enhanced viral growth characteristics in vitro. Differences in shedding efficacy and, as a result, differences in the amount of mature GP available for incorporation into budding virions did not equate to differences in overall release of viral particles. Likewise, data suggest that the resulting differences in the amount of mature GP on the cell surface led to variations in the GP content of released particles and, as a consequence, in infectivity. In conclusion, fine-tuning of the levels of EBOV GP expressed at the surface of virus-infected cells via GP sheddin
g plays an important role in EBOV replication by orchestrating the balance between optimal virion GP content and cytotoxicity caused by GP.

Basically, this study also shows that the phenotype of interest – rate of progression – which in turn will influence overall infectivity – can be increased, or decreased, on the basis of individual nucleotide substitutions.

It is superb to see such excellence by researchers focusing on the right questions. Congratulations to Volchkov team at the Université de Lyon, Université Claude Bernard, and the Institut für Virologie, Philipps-Universität Marburg, and the team led by Yang at Emory University, and the Atlanta VA Medical Center (Mohan et al.).

References

Dolnik et al., 2004. Ectodomain shedding of the glycoprotein GP of Ebola virus. EMBO J. 23:2175-2184.

Dolnik O.  et al., 2015. Shedding of Ebola virus surface glycoprotein is a mechanism of self-regulation of cellular cytotoxicity and has a direct effect on virus infectivity. J Infect Dis. pii: jiv268.

Mohan et al., 2015. Less Is More: Ebola virus surface glycoprotein expression levels regulate virus production and infectivity. J. Virology 89:1205-1217. jvi.asm.org/content/89/2/1205.full

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GUEST POST |Manuel Gea| Big Data: Big garbage? An estimated 85% of research resources are wasted!

bigdata

Manuel Gea

CEO BMSystems

This post appeared originally on Manuel’s LinkedIn pageI thought it important enough to invite as a Guest Blog Post on JAMESLYONSWEILER.COM  It is slightly edited for context. It is extremely relevant for ipaknowledge.org and there are lessons here for us all. Enjoy. JLW

New evidence published in Science confirms the poor reproducibility (less than 1/3) of studies published in peer-reviewed journals.

And, published by Stanford University in PLOS medicine, are findings that show that  many published research findings are false or exaggerated, and an estimated 85% of research resources are wasted (see publication 2 below).

The main objective of this post to launch a discussion and try to prevent big data to become only big garbage in life sciences. It is possible, but we need to work on the right concepts and methods.

What we really need to implement Mechanisms-Based Medicine should be: High value Smart Data. These “Mechanisms-Based Smart Data” to give real medical “sense” to what we measure. It means that they must necessarily be:

  1. Characterized, traceable and contextualized.
  2. Based on a robust biological mechanisms understanding, and
  3. Related to patients base-lines.

For 2015 we should not forget that: “In life sciences, with less than 10% success rate, a dominant recurrent thinking that repeatedly fails may be “false”!, even if supported by Key opinion leaders” if we want to start thinking out of the box!*

Many thanks for all the comments and questions on my previous posts about the issue of big data in life sciences especially for discovery..Find below 7 documents published of great interest that support and better explain my posts. Do not hesitate to join my network or send me feedback

  1. August 2015: A new evidence published in Sciences confirms the poor reproducibility (less than 1/3) of studies published in peer-reviewed.
  2. How to Make More Published Research True. Published in PLOS Medicine by John P. A. Ioannidis Meta-Research Innovation Center at Stanford (METRICS), Stanford University.
  3. Diagnosing the decline in pharmaceutical R&D efficiency. Published Nature Review Drug Discovery. The diagnostic is clear for our industry.
  4. Believe it or not: how much can we rely on published data on potential drug targets? Their title is crystal clear. Published Nature Review Drug Discovery.
  5. The Differences & Complementarities Between « Heuristic » and « Mathematical» approaches. The scientific presentation given by Dr. François IRIS (CSO BMSystems) during the EPA (European Psychiatric Association) conference in 2011.
  6. Psychiatric Systems Medicine success: Invited review in Pharmaco-Psychiatry to present the first Mechanisms-Based Medicine program that led to discoveries validated in-vivo: The late phase of the Creutzfeld-Jacob (Mad Cow) disease mechanisms was deciphered and the indirectly led to discovery of the novel therapy for psychiatric disorders
  7. The principles of Mechanisms-Based Medicine and 9 proof of concepts

*Thinking out of the box already contributed to the creation of two funded Pharma SMEs at clinical stage: Pherecydes-Pharma (2006, novel M.R. bacteria bio-therapies), Theranexus (2013, innovative combined therapies for Psychiatric disorders).

To contact Manual, email him at manuel.gea AT bmsystems.net .

IPAK Launch – Greater Pittsburgh Area, PA

Pittsburgh, PA. Sept 1, 2015. Author and research scientist James Lyons-Weiler, PhD has teamed up with other professionals from around the country to launch a new type of research institute that is designed to provide impartial research results and views on some of the most important and controversial topics in biomedicine, psychiatry, and sociology. Conducting science in a way that is independent of any profit motive – so the results can be better trusted – will be the core paradigm of the institute.

The Institute for Pure and Applied Knowledge (IPAK) is the first of its kind in the country. Research conducted by people who, under the by-laws, can have no financial stake in the outcome of the research will be IPAK_logo_jpgkey to insuring ethical, rigorous, objective, and impartial results for the studies they conduct. Putting knowledge at the center, instead of profit, will also allow the institute to keeping the cost of infrastructure down. As such, IPAK qualifies as a “pure public charity”. It will work with partner institutions in a manner keeping with the highest standards of scientific objectivity.

“This approach is innovative and definitively counterculture to the mainstream of for-profit research” says Dr. James- Lyons-Weiler, whose own career has stretched twenty years in basic, biomedical, and clinical research. He recently published a book “Ebola: An Evolving Story”, in which he analyzed all of the information coming from West African reports, US government and international agencies, and the media to objectively sort out fact from fiction. He used second book, “Cures vs. Profits: Successes in Translational Research”, due out in 2016, as a means to celebrate the many advances in biomedical research made possible by people conducting research with integrity.

The Institute will focus on numerous primary “Project Areas”, some of which are very important to people in Hampton Township and the greater Pittsburgh region. They include Accuracy in Treatments (e.g., inappropriate use of medicines in nursing homes), ADHD Overdiagnosis, Early Alzheimer’s Diagnosis and Treatment, Early Detection and Diagnosis of Emerging Diseases, Vaccine Safety Research, and factors contributing to Veteran’s Suicide.

“These are hard topics to study, but they affect so many people through public health policy and treatment options, they deserve rational, empirical studies conducted with much more objectivity than they have received to date” says Dr. Lyons-Weiler. Collaborating across institutions and areas of expertise will also be a key to insuring success in these areas. Lyons-Weiler says he learned about the high priority and the need for profit-free research in these areas while writing his second book.

“I discovered in researching my first book that many of our public health policies in response Ebola, and the actual practice of medicine in the fight against Ebola, are not always based on logic, or even based on fact, in many cases. For the second book, I interviewed experts in all of these research areas, and others, including cancer vaccines, and I found a core set of characteristics of research scientists whose work led to improvements in biomedicine. A focus on research integrity was at the core. The advances I review in the book are rock-solid.”

In an era of massive profits in medicine, and with news of scientific fraud increasing, the public has trouble trusting results from any particular study. “The profit motive biases researchers and institutions to specific interpretations – and millions of lives can be impacted when those biases obscure the actual signal in the data. In this era, profit-free objectivity is innovative – and IPAK is at the forefront of that innovation.”

Funding of IPAK will be through donations, foundations, grant support and memberships in SPAK, The Society for Pure and Applied Knowledge. IPAK scientists will compete for government and foundation grant funding in all of these areas.

Dr. Lyons-Weiler also hosted a fundraiser for the 16,600 orphans of Ebola in West Africa, which raised over $1,000 to help fund UNICEF to house orphans in West Africa. He says the epidemic was completely unnecessary. “We were told – quite frankly – that the reason why no vaccine had yet been developed was because there was no profit motive for companies to underwrite their development. IPAK researchers will work on critical developments to produce knowledge that can be used to reduce human pain and suffering – for its own sake.”

Other Project Areas include Compassion Use simplification (easing the burden of FDA paperwork for terminally ill patients seeking use of experimental drugs), FDA clinical trial reform, and colon cancer prevention.

IPAK headquarters will be located north of Pittsburgh, PA.

For more information, visit ipaknowledge.org

For questions about IPAK, contact jim@ipaknowledge d-o-t org